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Introduction: Platelets play an important role in the pathogenesis of COVID-19. Therefore, their parameters vary in different stages of the disease. The importance of plateletcrit in COVID-19 is not well known. Objective: To examine the diagnostic value of plateletcrit in COVID-19. Methods: From January to March and September-December 2021. during their initial visit to the COVID outpatient clinic at the Primary Healthcare Center Nis, we examined 440 patients who were experiencing possible COVID-19 symptoms. Following the examination, a complete blood count was performed, and they tested positive for COVID-19. We analyzed the plateletcrit in every lab sample collected during their first visit. The control group consisted of 60 patients from the "green zone" from January to December 2021, as well as 48 patients from the pre-COVID period, before 2020. Results: Lower plateletcrit was found in 48,4% of women and 63,3% of men in the first period. Out of the total of 111 patients, lower plateletcrit was found in 54,9%. in the second period lower plateletcrit was found in 72,2% of women and 85% of men. Out of the total number of 329 patients, lower plateletcrit was found in 78,7%. In the control group, from the "green zone" lower plateletcrit was found in 8,3% of 60 patients, and no decrease in plateletcrit levels was observed in 48 patients from the pre-COVID-19 era. Conclusion: Plateletcrit levels are decreased in many patients during their initial visit due to COVID-19. Symptoms. Therefore, variations in plateletcrit levels could raise concerns about potential COVID-19 infection.

Background/Aim. The cause of eosinophilia often remains unelucidated. The aim of the study was to analyze causes and treatment approaches in children with eosinophilia in pediatric tertiary care hospital. Methods. The medical records of children investigated for eosinophilia (based on the International Classification of Diseases code D72.1) were retrospectively reviewed in the University Children’s Hospital, Belgrade, Serbia, from December 2011 to December 2022. A total of 105 children (62 boys; male:female ratio was 1:4) aged one month to 16.5 years (median 7.7 years) were diagnosed with eosinophilia. After excluding 15 of them due to incorrectly assigned diagnosis based on relative eosinophil number only, the remaining 90 children were grouped according to the severity of eosinophilia (mild, moderate or severe). Results. Serological analysis con-firmed toxocariasis in six (6.7%) patients, while two (2.2%) had a confirmed nematode infestation (Ascaris lumbricoides and Enterobius vermicularis, respectively). Thirty-two (35.6%) children with eosinophilia and three with no true eosinophilia were diagnosed with helminthiasis ex juvantibus. Eosinophilia was ultimately explained by allergic/atopic conditions [19 (21.1%)], drug reactions [four (4.4%)], bacterial infections [nine (8.9%)], hematological problems [five (5.5%)], autoimmune disorders [three (3.3%)], unrelated congenital disorders (one), or as an isolated finding [seven (7.8%)]. In addition, one of the children without an increased absolute eosinophil number was diagnosed with eosinophilic esophagitis. A total of 56 (53.3%) children received anthelminthic treatment: 9 (90.0%) with severe eosinophilia, 19 (51.4%) with moderate, 23 (53.5%) with mild, and 5 (33.3%) children with no true eosinophilia. Most (42) of the children were given mebendazole only, while the remaining 14 (eight with severe, three with moderate, and three with mild) were also initially treated with mebendazole but subsequently shifted to albendazole due to the persistence of eosinophilia. In all treated children, eosinophilia and other relevant findings (if any) subsided in a matter of a few days to a few weeks after initializing treatment. Conclusion. Our results support the recommendation that unexplained eosinophilia of all levels of severity requires a standardized diagnostic approach. The results also provide some support for a potential rational basis for ex juvantibus administration of anthelminthic drugs in a fraction of children with eosinophilia without an obvious etiological explanation.

Ivana Stević,1 Nemanja Petrović,2 Slobodan M Janković2 1Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia; 2Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaCorrespondence: Slobodan M Janković, Faculty of Medical Science, University of Kragujevac, Svetozara Markovića street, 69, Kragujevac, 34000, Serbia, Email sjankovic@medf.kg.ac.rsAbstract: To satisfy the needs of pediatric and other patients with focal onset seizures who cannot swallow solid dosage forms of zonisamide, an oral liquid form of this drug is necessary in clinical practice. Although there are two oral suspensions of zonisamide with marketing authorization (MA), there are issues of availability and high cost which limit their use and inspire extemporaneous compounding. Extemporaneously compounded oral suspensions of zonisamide are prepared according to different formulas and vary in stability; therefore it is essential to test this characteristic. Bioequivalence of extemporaneously compounded oral suspensions has never been tested, and the efficacy and safety of zonisamide oral suspensions have generally not been demonstrated in clinical trials. As a narrow therapeutic window drug, zonisamide requires precision in dosing, which could be achieved only with dosage forms with established bioavailability, efficacy, and safety. In order to avoid underdosing and toxicity with zonisamide oral suspensions and utilize their full therapeutic potential, it is necessary to perform bioequivalence studies with each variation of extemporaneously compounded oral suspension and also clinical trials with both commercial and extemporaneous oral suspensions of zonisamide.Keywords: zonisamide, oral suspension, stability, bioequivalence

Background/Aim. A substantial line of evidence indicates that Kv4.2 and Kv4.3 channels are the major components of rapid transient-outward potassium currents (A-type cur-rents). It is speculated that those currents may be involved in the maintenance of the membrane potential, as well as in the regulation of propagation and frequency of action potentials. However, very little is known about the presence and function of A-type currents in human vascular smooth muscles such as the human umbilical vein (HUV). Bearing in mind its crucial role in the proper fetal oxygenation, the aim of the study was to determine whether Kv4.2 and Kv4.3 potassium channels are present in HUV smooth muscle and to investigate potential alterations of their expression during maternal pathological conditions such as gestational diabetes mellitus (GDM) and pregnancy-induced hypertension (PIH). Methods. Healthy, diabetic, and hypertensive pregnancies were subjects of this investigation. Each group consisted of 6 HUV samples obtained from 6 normal pregnancies, 6 pregnancies with GDM, and 6 with PIH. After pharmacology analysis, immunohistochemistry (IH) and Western blot were performed. Results. IH revealed similar expression patterns of both, Kv4.2 and Kv4.3 subunits in HUV smooth muscle in all groups of patients. Results obtained by Western blot were in agreement with IH staining. The expression of Kv4.2 and Kv4.3 subunits were not significantly different between the groups. Conclusion. Collective-ly, this is the first study that demonstrated the presence of Kv4.2 and Kv4.3 potassium channels in the HUV smooth muscle and their preservation during GDM and PIH pregnancies. These channels are most likely major components of rapid A-type currents that may be relevant for maternal-fetus blood flow and hence fetal development. In addition, they may represent sensors for detecting hemodynamic and/or metabolic changes in the local environment.

Introduction. Schimke immuno-osseous dysplasia (SIOD) is a rare autosomal recessive multisystem disorder associated with biallelic mutations of the SMAR-CAL1 gene. Vascular central nervous system complications in the form of Moyamoya syndrome (MMS) have been reported as a comorbidity in nearly half of the patients clinically presenting with severe migraine-like headaches, transient ischemic attacks (TIA), and ischemic or hemorrhagic infarctions. We present an illustrative case of an infantile form of SIOD with MMS, with a review of the latest diagnostic possibilities, as well as current diagnostic and therapeutic dilemmas in managing SIOD. Case report. We present a female patient with the infantile form of SIOD. The proband was born small for gestational age in the 34th gestation week with characteristic dysmorphic features. Genetic testing found a biallelic, nonsense mutation c.2542G>T in the SMARCAL1 gene. The patient presented early with TIA, seizures, and recurrent ischemic strokes. Magnetic resonance imaging (MRI) confirmed the presence of progressive brain atrophy with bilateral occlusion/stenosis of middle cerebral artery and anterior cerebral artery and a smoke-like collateral vessel appearance consistent with the MMS. At the age of 5 years and 9 months, the patient developed a high fever and cough with unknown cause, with a low erythrocyte and white blood cell count during four weeks, with a poor therapeutic response to antibiotics, transfusion of red blood cells, and granulocyte growth factor. She later died. Conclusion. Patients with SIOD may present progressive cerebral vascular changes and clinical neurologic deterioration early in the course of the disease. In such patients, early diagnosis and preventive revascularization surgery are of paramount importance. In diagnosing MMS, MRI angiography can be an appropriate substitute for standard invasive cerebral angiography.

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Background/Aim. Asthma is a chronic inflammatory lung disorder. The effect of asthma drugs on oral health is still the subject of debate among researchers in dentistry. The aim of this study was t o e valuate dental status in asthmatic children and evaluate the possible effect of drugs treating asthma on dental health. Methods. Study participants were divided into two groups: the asthma (AG) and the non-asthma (NAG) group. Based on the symptoms of asthma and the possibility for effective control of the disease, the AG group was divided into two subgroups. The oral examination of the teeth was per-formed using a probe and mouth mirror under artificial light in accordance with the recommendations of the World Health Organization. Saliva analysis was carried out by the GC Saliva-Check Buffer, according to the manufacturer's instructions. Results. The study included 136 children aged 6 to 16 years (10.5 ± 3.3). The mean of decayed, missing, and filled teeth (dmft/DMFT) of the children in the AG group (6.0 ± 4.0/3.3 ± 4.4) was higher than in the NAG group (4.8 ± 4.4/2.5 ± 3.4), but significant differences were not observed between the groups. Salivary pH values were found to be similar in both groups, but the quantity and buffering capacity of the stimulated saliva were found to be significantly lower in the AG group (p < 0.001 and p < 0.05, respectively). Conclusion. Although the prevalence of dental caries in the AG group was similar to that of the NAG group in this study, decreased quantity and buffering capacity of the stimulated saliva in the A G group may contribute to higher values of dental caries in asthmatic children in the future.

Background/Aim. Despite the widespread use of procalcitonin, C-reactive protein (CRP), and soluble CD14 subtype (sCD14-ST), their diagnostic accuracy in children with sepsis is not yet clear. The aim of the study was to establish and compare the diagnostic accuracy of procalcitonin, CRP, and sCD14-ST in children admitted to the hospital under suspicion of having sepsis. Methods. The study was designed as a retrospective cross-sectional study on children admitted to the Pediatrics Clinic in Kragujevac, Serbia, under suspicion of sepsis, during a 6-month period. Diagnostic accuracy was tested by the construction of receiver operating characteristic (ROC) curves and their comparison in terms of area under the curve (AUC). Results. Procalcitonin had the largest AUC [0.75; 95% confidence interval (CI) 0.63–0.88], followed by CRP (0.68; 95% CI 0.54–0.81) and sCD14-ST (0.65; 95% CI 0.52 – 0.79). Differences between the areas under the ROC curves were not significant (CRP vs. procalcitonin z = 1.054, p = 0.291; CRP vs. sCD14-ST z = 0.238, p = 0.812; procalcitonin vs. sCD14-ST z = 1.089, p = 0.286). Conclusion. Our study showed relatively low sensitivity and moderate specificity of procalcitonin, C-reactive protein and sCD14-ST in diagnosing sepsis among children, as well as similar diagnostic accuracy of the three biomarkers.

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Bacground/Aim. Treatment of neurological diseases usually requires polypharmacy, and it is crucial to detect potential drug-drug interactions (DDIs) and recognize risk factors on time, as consequences of DDIs could be serious. The aim of the study was to analyze risk factors for the occurrence and the number of potential DDIs among patients in a general neurological ward. Methods. This study was conducted with 144 inpatients in a general-care neurological department of a tertiary care hospital. The effects of risk factors for potential DDIs were evaluated by multiple linear regression. The study had retrospective cohort de-sign. Frequencies of various types of potential DDIs (according to severity) were discovered by Medscape, Epocrates and Micromedex online interaction checkers. Results. The number of prescribed drugs, age of a patient, value of the Charlson comorbidity index and prescription of an antidepressant increase risk of potential DDIs in a general neurology ward. On the other hand, being paralyzed, number of prescribers for a single patient, being bedridden for at least one day of hospitalization decreased the number of potential DDIs per patient. Number of prescribed drugs per patient [odds ratio (OR) = 1.466 ± 0.250; p = 0.000) and age (OR = 1.027 ± 0.026; p = 0.041)] increased, and number of prescribers per patient (OR = 0.056 ± 0.028; p = 0.016), especially if the patients were paralyzed (OR = 0.214 ± 0.294; p = 0.007), decreased the risk of contraindicated, serious, “use alternative” or major potential DDIs. Antidepressants increased the risk of absolute number of all monitor/modify potential DDIs (OR = 1.257 ± 0.726; p = 0.035). Conclusion. Frequency of potential DDIs among neurological patients is considerable and influenced to the largest extent by advanced age, comorbidities, total number of pre-scribed drugs per patient and concomitant use of antidepressants.

Backgroun/Aim. Although majority of guidelines recommend triazoles (voriconazole, posaconazole, itraconazole and isavuconazole) as first-line therapeutic option for treatment of invasive aspergillosis, echinocandins (caspofungin, micafungin and anidulafungin) are also used for this purpose. However, head-to-head comparison of triazoles and echinocandins for invasive aspergillosis was rarely target of clinical trials. The aim of this meta-analysis was to compare efficacy and safety of triazoles and echinocandins when used for treatment of patients with invasive aspergillosis. Methods. This meta-analysis was based on systematic search of literature and selection of high-quality evidence according to pre-set inclusion and exclusion criteria. The literature search was made for comparison of treatment with any of triazoles (isavuconazole, itraconazole, posaconazole or voriconazole) versus any of echinocandins (caspofungin, anidulafungin or micafungin). The effects of triazoles (itraconazole, posaconazole or voriconazole) and echinocandins (caspofungin, anidulafungin or micafungin) were summarized using RevMan 5.3.5 software, and heterogeneity assessed by the Cochrane Q test and I² values. Several types of bias were assessed, and publication bias was shown by the funnel plot and Egger’s regression. Results. Two clinical trials and three cohort studies were included in this meta-analysis. Mortality in patients with invasive aspergillosis who were treated with triazoles was significantly lower than in patients treated with echinocandins [odds ratio 0.29 (0.13, 0.67)], and rate of favorable response (overall treatment success) 12 weeks after the therapy onset was higher in patients treated with triazoles [3.05 (1.52, 6.13)]. On the other hand, incidence of adverse events was higher with triazoles than with echinocandins in patients treated for invasive aspergillosis [3.75 (0.89, 15.76)], although this difference was not statistically significant. Conclusion.Triazoles (voriconazole in the first place) could be considered as more effective and somewhat less safe therapeutic option than echinocandins for invasive aspergillosis: However, due to poor quality of studies included in this meta-analysis, definite conclusion should await results of additional, well designed clinical trials.

Background/Aim. Liver damage, with potentially serious consequences, is not uncommon in hospitalized cardiac patients. The aim of our study was to determine the risk factor profile for liver damage in patients hospitalized from a deterioration of their acute or chronic cardiac illness. Methods. The study had observational case-control design with retrospective data collections from medical files of adult patients hospitalized in a tertiary health care center. The cases (n = 140) were subjects with novel liver injury (which emerged during hospital stay) and three control subjects were matched (age, date) for each case subject (n = 420). The primary outcome was hepatotoxicity (present or absent) and independent variables were proposed risk factors. Statistical analysis included descriptive methods, hypothesis testing and univariate and multivariate binary logistic regression, with p ≤ 0.05. Results. In the whole study population, there were 432 (77.1%) females and the mean age of patients was 64.1 years [standard deviation (SD) = 10.7, range 24–85 years]. The most common illnesses were coronary heart disease (n = 385), hypertension (n = 334) and arrhythmia (n = 115). Mean value of Charlson Comorbidity Index (CCI) score was 3.8 (SD=1.7; range 1-10) corresponding to estimated CCI 10-years survival rate of 54.4% (SD = 33.5%). In the group of cases, 114 (81.4%) of the patients had hepatocellular, 9 (6.4%) cholestatic and 17 (12.2%) mixed type of hepatic injury. Factors independently associated with hepatotoxic event were previous occasional alcohol intake odds ratio (OR) 96.47; 95% confidence interval (CI) 28.95–321.43; p < 0.001), amiodarone (OR 3.70; 95% CI 1.82–7.53; p < 0.001), enoxaparin (OR 3.29; 95% CI 1.79–6.05; p < 0.001), obesity (OR 2.78; 95% CI 1.15– 6.71; p < 0.023), atorvastatin (OR 2.67; 95% CI 1.33–5.38; p < 0.006) and CCI total score (OR 1.89; 95% CI 1.53–2.34; p < 0.001). Conclusion. Major factors associated with acute liver damage in patients hospitalized in cardiology ward of a tertiary health care institution were patient’s constitutional and habitual characteristics (occasional alcohol intake, obesity, CCI total score) and drugs with known hepatotoxic properties (amiodarone, enoxaparin, atorvastatin).

Background/Aim. After having established an indication for surgery, some patients experience sense of fear, unpleasantness and embarrassment due to the expectance of adverse consequences of surgical intervention. Recently an instrument for measuring fear of surgery – the Surgical Fear Questionnaire (SFQ) – was developed and validated on a sample of Dutch patients awaiting surgery. The objective of this study was to translate the SFQ to Serbian language, make cultural adaptation of the translation and test its reliability and validity in a sample of outpatients in Serbia. Methods. The SFQ was translated and adapted according to the accepted international standards (double forward translation, harmonization, backward translation, and piloting). The study was multicentric, involving patients from 7 cities in 3 countries: Serbia, Montenegro, Bosnia and Hercegovina. It was conducted at state-owned health facilities. The sample was of consecutive nature and consisted of 330 outpatients who visited specialists of either internal medicine or general surgery. Results. Translated SFQ showed excellent reliability, both when rated by the investigators (Cronbach’s alpha 0.915), and by the patients themselves (Cronbach’s alpha 0.917). It is temporally stable, and both divergent and convergent validity tests had good results. Factorial analysis revealed one domain on the whole study sample and two domains like in original on the subsample of patients without experience with surgery in general anesthesia. Conclusion. Identification of patients with high level of fear of surgery by this questionnaire should help clinicians to administer measures which may decrease fear and prevent avoidance of absolutely necessary surgery by such patients.

Bacground/Aim. Preterm birth is defined as a delivery prior to the completed 37th week of gestation. Literature data suggested that periodontal processes may influence to the feto-placental unit and induce preterm delivery. The degree of the periodontal disease is influenced by secretor status. Pro-inflammatory cytokines are involved in periodontitis as well as in delivery. The combined influence of these factors on the risk of preterm birth has not been explored. The aim of our study was to investigate the associations between periodontal diseases, secretor status, and interleukin- 1-β (IL1-ß) and prostaglandine E2 (PGE2) levels in women delivered preterm. Methods. The study included 56 preterm delivery women and 56 women delivered at term as a control group, aged between 17 and 41 years. Periodontal examination, blood and saliva sampling were performed within 48 hours following delivery. Secretor phenotype was determined by hemagglutination inhibition method. The concentrations of IL1-ß and PGE2 were measured by high sensitivity Enzyme-linked Immunosorbent Assay (ELISA). Results. In the pre-term birth group there were 66.1% of women with periodontitis, while in the control one there were 12.5% (p < 0.01). Concentrations of IL1-ß and PGE2 in plasma were significantly higher in the non-secretor group of women who gave birth pre-term and had periodontitis comparing to other groups. There was a significant correlation between salivary and plasma levels of PGE2 and IL1-ß in the preterm birth group (R = 0.416, p = 0.017 and R = -0.592, p < 0.001, respectively). There were no such correlations in women who delivered at term. Conclusion. Our results support the hypothesis that non-secretor phenotype and periodontitis are at least in part responsible for pathogenesis of preterm birth. This probability of negative impact of non-secretor status cannot be ignored. These findings support the need for additional research into the biology of human parturition.

Background/Aim. Nausea after oral administration of iron is frequent phenomenon (11% of patients) and it is believed to be consequence of accumulation of free radicals in mucosa of gastrointestinal tract. The aim of our study was to measure the extent of nausea in outpatients taking oral supplementation with iron, and to investigate possible factors that may have an influence on it. Methods. The study was of the cross-sectional type, and conducted on a sample of outpatients on oral iron supplementation. The sample was consecutive, including all patients coming to a community pharmacy for oral iron supply during the study period. Frequency and severity of nausea were measured by the 5- item Drug-Induced Nausea Scale (DINS). Results. The mean score of the DINS from the sample of 128 patients was 8.56 ± 5.07 (range from 5 to 25). Each additional cup of coffee per week increased the DINS score for 0.143 points, the history of gastrointestinal disease had protective effect and decreased the DINS score for 5.923 points. Conclusion. Frequency and severity of oral iron-induced nausea are not dependent on oral iron burden, but rather on coffee intake and previous experience of patients with symptoms of gastrointestinal diseases. Modification of diet and education about types and severity of symptoms of gastrointestinal diseases could be useful preventive measures to avoid or at least mitigate oral iron-induced nausea and/or vomiting.

Background/Aim. The two-part questionnaire called Injection Phobia Scale (IPS)-Anxiety and IPS-Avoidance represents one of the most commonly used questionnaires for assessing the fear of injections. The aim of the present study was to translate and culturally adapt this questionnaire from English into Serbian as well as to assess reliability and validity of the translation. Methods. The translation and cultural adaptation of the IPS–Anxiety and IPS–Avoidance was performed in accordance with the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) guidelines. Reliability testing, factor analysis and validation of Serbian translation of IPS-Anxiety and IPS-Avoidance were carried out on a sample of 485 students of pharmacy, or medicine at the University of Kragujevac, Serbia. Results. Serbian translation of IPS-Anxiety and IPSAvoidance demonstrated high internal consistency with Cronbach’s alpha of 0.934 for IPS-Anxiety and 0.911 for IPS-Avoidance. Factor analysis of IPS-Anxiety showed that there are two domains, which we have called as Direct Experience (9 items) and Indirect Experience (9 items); factor analysis of IPS-Avoidance also pointed out on two domains referring to direct and indirect fear of injections. Female students scored higher on the scale showing more extensive injection phobia than male students. It is also interesting that students of pharmacy have higher level of injection phobia than students of medicine, and those students of the fifth year of study feel more fear of injections than students from the first four years. Conclusion. Serbian translation of IPS-Anxiety and IPS-Avoidance showed good psychometric properties on population consisted of students medicine and pharmacy. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175007]

Background/Aim. There are several questionnaires for measuring intensity of nausea after drug administration, but they are either too settings specific (like those measuring chemotherapy-induced nausea), or they were not properly tested for reliability and validity. The aim of this study was to develop and validate a reliable instrument that can measure drug-induced nausea. Methods. The cross-sectional study for assessing reliability and validity of a questionnaire was performed. The questionnaire with 5 items and answers according to the Likert’s scale was developed during two brainstorming sessions of the research team. Its reliability, validity and temporal stability were tested on the sample of 128 outpatients taking iron salts orally. Results. The final version of the Drug-Induced Nausea Scale (DINS) with 5 items showed excellent reliability, both when rated by the investigators (Cronbach’s alpha 0.892) and by the patients themselves (Cronbach’s alpha 0.897). It was temporally stable, and both divergent and convergent validity tests had very good results. Factorial analysis revealed only one factor, which means that the whole scale is measuring only one phenomenon, intensity of nausea, as was originally intended. Conclusion. The DINS is reliable and valid instrument for measuring intensity of drug-induced nausea. Identification of patients with high intensity of druginduced nausea by this questionnaire will help prescribers to decide whether the therapy should be stopped or the patient switched to less emetogenic therapy.

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Background/Aim. Inappropriate prescribing of antibiotics to the patients with acute bronchitis is frequent event in clinical practice with potentially serious consequences, although majority of treatment guidelines do not recommend it. The aim of this study was to reveal risk factors associated with inappropriate prescribing of antibiotics to the patients with acute bronchitis in primary healthcare. Methods. This case/control study included the adult patients with acute bronchitis during the initial encounter with a general practitioner. Prescription of an antibiotic was an event that defined the case, and patients without prescribed antibiotic served as controls. Results. Antibiotics (mostly macrolides and beta-lactams) were prescribed to the majority of patients with diagnosis of acute bronchitis (78.5%). A significant association was found between antibiotic prescription rates and patient age, whether an attending physician is a specialist or not and the average number of patients a physician sees per day [ORadjustedwas 1.029 (1.007–1.052), 0.347 (0.147–0.818) and 0.957 (0.923–0.992), respectively]. Conclusion. When there is primary care encounter with patients suffering from acute bronchitis, older patients are more likely to receive inappropriate antibiotic prescription, especially if their physician is without specialist training and has less patient encounters in his/her office daily.

Background/Aim. The Headache Under-Response to Treatment (HURT) questionnaire and the Migraine Disability Assessment Test (MIDAS), which are intended for assessing the headache-related disability, impact (MIDAS) and management (HURT), were not yet translated to Serbian and validated in the population of Serbia. The aim of this study was to translate the HURT and MIDAS from English to Serbian, to make necessary cultural adaptations and to test their psychometric properties in a sample of outpatients with the headache. Methods. The HURT and MIDAS questionnaires were translated and adapted according to the internationally accepted guidelines, and then tested on a sample of Serbian patients with various headache types. Internal consistency was checked through the calculation of Cronbach’s alpha for the questionnaires, and by correlation of each question with the corrected total score. The criterion validity of the translation was tested by correlating scores of individual items, domains and whole questionnaire with the headache characteristics (severity, duration, frequency), and convergent validity was tested by correlating the abovementioned scores with results of an instrument for measurement of headache-related quality of life. Results. There were 171 (79.2%) females and 45 (20.8%) male study participants. The mean age of the patients was 42.3 years, (standard deviation – SD 13.35; range 18–75); 27 (12.5%) suffered from a migraine and 189 (87.5%) from the episodic tension-type headache (TTH). The Serbian translation of HURT and MIDAS questionneires showed excellent internal consistency, with high values of the Cronbach’s alpha: 0.764 and 0.731, respectively. The validity of the instruments in all aspects (criterion, convergent and discriminant validity) was also excellent for the whole sample and for the subgroup of patients with TTH, while the results for the patients with the migraine were less favorable. The factor analysis suggested the existence of one domain of MIDAS and two domains of HURT questionneires. Conclusion. The Serbian translations of HURT and MIDAS could be used as the reliable and valid specific instruments for measuring a headache-related disability, impact (MIDAS) and management (HURT) in the patients with TTH and probably in the patients with the migraine. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175007]

Background/Aim. Oral health is an important part of overall health. Good oral health is important for oral diseases prevention and health maintenance of respiratory system. The aim of the study was to evaluate oral hygiene and periodontal health parameters of asthmatic children and to compare them with children without asthma as well as to evaluate those parameters according to type of used medications and time of taking medications in children with asthma. Methods. This epidemiological study included 68 children with asthma and 68 children without asthma or any other chronic disease aged from 6 to 16 years. Parameters used in this study were Greene-Vermillion index, Löe-Silness gingival index and Community Periodontal Index (CPI). Results. Good oral hygiene (31.1%) was more present in children without asthma whereas poor hygiene (20.0%) was more frequent in children with asthma (p < 0.001). Healthy gingiva was more frequent in children without asthma (25%) while mild (58.8%) and moderate gingival inflammation (5.9%) were more frequent in the group of children with asthma (p < 0.01). Mean CPI values were higher in children with asthma (p < 0.001). Mean values of Plaque Index, Gingival Index and CPI did not show statistically significant difference in relation to type of administered medication. However, taking medications in the afternoon was related to higher mean values of Plaque Index and Gingival Index (p < 0.05) within the group of children with asthma. Conclusion. Children with asthma had poorer oral hygiene and were diagnosed with greater values of oral hygiene and periodontal indices compared with the group of children without asthma. For this reason, it is necessary to promote oral health and establish good oral hygiene habits in asthmatic children.

Background/Aim. Reslizumab is humanized monoclonal antibody produced by recombinant DNA technology which binds to circulating interleukin-5 (IL-5) and down-regulates the IL-5 signaling pathway. Reslizumab is indicated for the add-on maintenance treatment of patients 18 years and older with severe eosinophilic asthma phenotype whose symptoms were inadequately controlled with inhaled corticosteroids. The aim of this meta-analysis was to assess the efficacy and safety of reslizumab compared to placebo in patients suffering from inadequately controlled, moderateto- severe asthma with elevated blood eosinophil counts. Methods. Our meta-analysis was based on systematic search of literature and selection of high-quality evidence according to pre-set inclusion and exclusion criteria. The effects of reslizumab and placebo were summarized using Review Manager (RevMan) 5.3.5 and heterogeneity was assessed by the Cochrane Q test and I² values. Several types of bias were assessed and publication bias shown by Funnel plot and Egger’s regression. Results. The meta-analysis included 5 randomized, placebo-controlled clinical trials. Reslizumab 3.0 mg/kg produced substantial improvements in forced expiratory volume in 1. second (FEV 1) (mean difference 0.15 [0.10, 0.21]) and in forced vital capacity (FVC) (mean difference 0.21 [0.09, 0.32]) over the 15 or 16-week treatment period, substantial decrease versus placebo in Asthma Control Questionnaire (ACQ) score (mean difference -0.28 [-0.41, -0.16]), and substantial increase vs. placebo from baseline in Asthma Quality of Life Questionnaire (AQLQ) total score (mean difference 0.24 [0.06, 0.43]). Also, reslizumab 3.0 mg/kg caused less adverse events versus placebo (OR 0.67 [0.51, 0.88]), especially asthma worsening (OR 0.53 [0.36, 0.77]) or bronchitis (OR 0.42 [0.24, 0.74]). Conclusion. On the basis of published clinical trials reslizumab could be considered as an effective and safe therapeutic option for severe, poorly controlled eosinophilic asthma for the time being. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. 175007]

Backgraund/Aim. Increased body weight in childhood may have negative effects on many tissues and organs in the body. The aim of this study was to determine whether the state of oral health in children with increased body mass is different from the children with normal body weight. Methods. The study included 190 children, aged 6 to 15 years. Assessment of nutritional status of subjects was performed by the use of Body Mass, and the respondents were divided into a group of increased body weight children (IWC) and a group of normal body weight children (NWC). Hard dental tissue state of health was assessed by the decayed, missing and filled teeth (DMFT) index. The gingival health was assessed using gingival index (GI). Community Periodontal Index (CPI) was used for the assessment of periodontal tissue. The oral hygiene was assessed using the Simplified Debris (Plaque) Index Greene-Vermilion. Results. Average DMFT value in the IWC group was 5.01 ± 2.4, and in the NWC 4.43 ± 2.0; (p > 0.05). GI values in the IWC group was 0.64 ± 0.37, while in the NWC group it was 0.55 ± 0.35 (the difference was not statistically significant). Average CPI index values were 1.33 ± 0.49 in the IWC group and 0.77 ± 0.61 in the NWC group and statistically significant differences were observed concerning periodontal tissue state of health. The GV index values in the IWC group were 1.01 ± 0.49, and in the NWC group 0.89 ± 0.45; it was not statistically significant. Conclusion. Results of this research do not indicate that children with increased body weight have more affected teeth. However, they have a worse condition of periodontal tissue in comparison to normal weight children.

Background/Aim. Quality of life in patients early after elective surgery is related to postoperative pain and recovery rate. The aim of this study was to compare immediate preoperative and early postoperative quality of life after three common elective surgical interventions in hospital settings. Methods. Population of this prospective cohort study included patients who underwent one of the three surgical interventions: elective laparoscopic cholecystectomy (n = 40), open inguinal hernia repair (n = 40) or excision of pilonidal sinus (n = 40). Primary outcome of the study was quality of life measured once-daily, starting from the day before surgery, and then each postoperative day. It was measured by visual analogue scale (VAS) and by Serbian translation of short questionnaire on quality of life developed by World Health Organization. Results. Postoperative quality of life dropped to the lowest level on the first postoperative day, regardless of the type of surgery. The drop was the most pronounced in physical and psychological aspects of quality of life (e.g. after cholecystectomy from 15.4 ± 2.5 to 12.5 ± 2.0, and from 15.9 ± 2.0 to 14.9 ± 2.1, respectively) while social and environmental aspects were the least affected by the surgery (e.g., after excision of pilonidal sinus from 16.3 ± 2.6 to 15.7 ± 2.1, and from 14.3 ± 2.6 to 14.1 ± 2.2, respectively). Quality of life was rapidly restored on the second postoperative day, and on the last day before discharge of the patient from hospital it surpasses preoperative level (e.g., after open inguinal hernia repair from 14.6 ± 3.6 to 15.2 ± 3.0. Conclusions. Minor elective surgical interventions are associated with only moderate (less than 25%) and short (one day) immediate postoperative decrease in quality of life, which is followed by increase on discharge from hospital to the levels, higher than preoperative one.

Introduction. Streptococcus pneumoniae is the second most common cause of meningitis in children, producing more serious complications than other bacteria. Streptococcus pneumoniae infections are a rare trigger of glomerulonephritis. We presented a case of glomerulonephritis developing concurrently with meningitis in a young male child. Case report. Gross haematuria, significant proteinuria, hypertension and decreased level of C3 alongside the signs of central nervous system involvement occurred in a male patient of 5 years and 3 months of age. Spontaneous resolution of renal affliction parameters followed the successful treatment of meningitis. The disease course was strongly suggestive of postinfectious glomerulonephritis, although it manifested at the same time as meningitis. The absence of the latent period might point to the development of IgA nephropathy, but since the renal function was stable, without any abnormalities in urine tests documented during follow-up, our opinion is that this was rather the case of postinfectious nephropathy. Conclusion. The presented case is a unique clinical form of postinfectious glomerulonephritis. An accurate diagnosis of this entity should ensure the adequate treatment and follow-up of these patients.

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Introduction. During the last few years, intravenous lipid emulsions have been effectively used in treatment of acute poisonings with lipophilic substances, including verapamil. Case report. A 37-year-old women presented 1 hour after ingestion of 2.8 g verapamil with hypotension and complete heart block. Because of the applied standard therapy failure and further patients impairment, Intralipid® 20% was used. Sinus rhythm was restored, arterial blood pressure increased and verapamile concentrations, both total and free decreased. Conclusion. Intravenous lipid emulsion can be important in treatment of severe acute intoxication and cardiotoxicity caused by verapamil.

Background/Aim. Data about effects of antidepressant on calcium, phosphorous and magnesium metabolisms are very scorce. The aim of this study was to investigate effects of antidepressants on serum concentration of bone metabolism markers and main electrolytes in patients from routine psychiatric practice. Methods. A prospective, before-and-after, time-series research included 9 males and 24 females, with average 53.3 ± 11.5 years-of-age, suffering from depression (n = 26) and neurotic disorders (n = 7), mostly taking selective serotonin reuptake inhibitors. We measured analytes at baseline, and 4th, 6th and 12th weeks during the treatment and tested the parameter changes from baseline and the trends with appropriate statistics at p ≤ 0.05 significance level. Results. The age above 60 years was a significant factor for appearance of negative cumulative changes (in percent) of 25-hydroxyvitamin D – 25(OH)D concentrations from the base-line (OR = 11.4, 95% CI 1.2–113.1, p = 0.037). Serum concentrations of calcium significantly correlated with sodium (rs = 0.531, p < 0.001), with chloride (r = 0.496, p < 0.001), with magnesium (rs = 0.402, p < 0.001) and with osteocalcin (r = 0.240, p = 0.019). Significant correlations were among phosphorous with chloride (r = -0.218, p = 0.035); magnesium with sodium (r = 0.295, p = 0.004) and with potassium, (r = 0.273, p = 0.009); osteocalcin with C-telopeptide (r = 0.760, p < 0.001) with sodium (r = 0.215, p = 0.039) and with chloride (r = 0.209, p = 0.041); sodium with chloride (r = 0.722, p < 0.001). There were no statistically significant changes between antidepressant treatment and changes of absolute serum concentration of calcium, magnesium, phosphorous, 25(OH)D, osteocalcin, C-telopeptide, sodium, potassium and chloride. There were no statistically significant changes in frequency of disturbances in values of laboratory analytes (below/above lower/upper normal limits), too. Conclusion. Antidepressant treatment was not significantly associated with the changes in study analytes but some of them positively correlated with each other, suggesting the need for individual patient approach and further research in the field of bone metabolism in patients with mental disorders.

Introduction. Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially life-threatening, hyperinflammatory syndrome caused by severe hypercytokinemia due to a highly stimulated, but ineffective immune response. Case report. We reported a 19-year-old woman presenting with fever, muscle and joint pain and sore throat. After diagnostic procedures we made the diagnosis of hemophagocytic lymphohistiocytosis (7 of 8 HLH-2004 diagnostic criteria) caused by Ebstein-Barr viral infection and trigerred by the intense physical activity. Genetic analysis showed three different sequence changes in Munc-18-2, two splice acceptor side mutations/changes affecting exon 10 (c.795–4 C > T) and exon 15 (c.1247–10 C > T) and a missense mutation c.1375 C > T; p.Arg 459 Trp. All mutations were in heterozygous state and their significance in pathogensis of HLH is not clear. After treatment with corticosteroids and cyclosporin A complete clinical remission was achieved. Conclusion. The presented case history suggests the possibility that mutations of undetermined clinical significance in a gene associated with primary HLH may underlie some cases of secondary HLH, probably by causing a partial, rather than total or subtotal, impairment of encoded protein function. Our case also suggests that strenuous physical activity (in apparent synergy with viral infection) can trigger HLH.

Introduction. Henoch-Schönlein purpura (HSP) is a small blood vessel vasculitis, which usually manifests during childhood. The exact cause of the disease is unknown. Case report. We reported a 14-year-old girl who had been admitted to our clinic due to the appearance of red macules on her extremities and face, vomiting, and pain in the abdomen and joints. The patient was initially diagnosed with Henoch- Schönlein purpura. At the end of the fourth week of illness, larvae of Strongyloides stercoralis were detected in stool samples. The patient was therefore treated with mebendazole, after which all symptoms permanently withdrew. About a month later laboratory examinations were repeated demonstrating increasing signs of renal damage. Kidney biopsy was performed, showing mesangioproliferative glomerulonephritis with crescents and IgA and C3 positive staining in the mesangium. Upon reviewing the clinical presentation, biochemically demonstrated progressive renal damage and biopsy results, the patient was diagnosed with HSP nephritis. Conclusion. The time course of the disease and present knowledge concerning the pathogenic mechanisms of HSP suggest that Strongyloides stercoralis infection could have caused HSP in the presented patient, which was complicated by nephritis.

Background/Aim. Urinary tract infections (UTIs) are among the most common infections in outpatients. The aim of this study was to define the causative agents of urinary tract infections and their resistance to antimicrobial drugs in the urban area of central Serbia, as well as to evaluate eventual differences associated with age and gender of the patients. Methods. This retrospective study analysed data taken from routine, consecutively collected urine cultures of outpatients with symptomatic UTIs, collected from the Department of Microbiology, Institute of Public Health in Kragujevac, Serbia, from January 2009 to December 2013. Results. There were 71,905 urine cultures, and 24,713 (34.37%) of them were positive for bacterial pathogens. The most common pathogen was Escherichia coli (E. coli) (56.56%), followed by Klebsiella spp. (16.20%), Proteus spp. (14.68%), Enterococcus spp. (5.29%) and Pseudomonas aeruginosa (3.74%). E. coli and Enterococcus spp. isolation rates were lower in males ≥ 60 years old (23.71% and 4.87%, respectively), while Klebsiella spp. was more prevalent in this group (32.06%). The most common causative agents isolated from 15–29 years old male patients were Enterococcus spp. and Pseudomonas aeruginosa (13.28% each). Among women, the isolation rate of E.coli was high in all age groups (around 70%). Proteus spp. was frequently isolated from females ≤ 14 years old (13.27%), while Klebsiella spp. was the most frequent in the oldest age female group (10.99%). Conclusion. Choice of antibiotics for treatment of UTIs should be governed not only by the local resistance patterns, but also by gender and age of patients.

Background/Aim. In the current literature, data on impact of intrahospital changes in patients’ nutritional status on the treatment outcome are limited. The aim of this study was to investigate the relationship between nutritional status deterioration and the treatment outcome among hospitalized gastroenterological patients. Methods. In 650 adult gastroenterological patients nutritional status on admission and at discharge was evaluated using the 6 nutritional status assessment parameters: body mass index, triceps skinfold thickness, mid-upper arm muscle circumference, serum albumin concentration, lymphocyte count and unintentional weight loss. The influence on treatment outcome was tested for the nutritional status on admission, nutritional status at discharge and intrahospital nutritional status deterioration. Results. The incidence of favorable outcome in the non-undernourished and undernourished patients on admission was in the range 93.4-97.3% and 81.2- 91.2%, respectively. The incidence of favorable outcome in the non-undernourished and undernourished patients at discharge was in the range 94-97.4% and 80.8-88.1%, respectively. Favorable outcomes were obtained in 95.6-98.9% of the patients without nutritional status deterioration and in 87.1-90.3% of the patients with nutritional status deterioration. Intrahospital nutritional status deterioration significantly influenced the outcome, no matter what assessment parameter had been used (p < 0.001 for all the applied parameters). Furthermore, only the deterioration of nutritional status was found to be an independent predictor of treatment outcome (multivariate analysis Forwald Wald, p £ 0.001; relative risk (RR) = 0.104-0.350; confidence intervals (CI) = 0.037-0.186/0.297-0.657). Conclusion. Deterioration of nutritional status is an independent predictor of adverse outcome.

Background/Aim. Drug-related problems are especially frequent among patients suffering from non-communicable diseases, like osteoporosis, leading to suboptimal treatment response. The aim of this study was to identify drug-related problems in patients with osteoporosis. Methods. This cross-sectional prospective study was conducted in January 2014 on outpatients with osteoporosis from three health facilities in Belgrade, Serbia. The patients included in the study were older than 50 years, and they were offered an anonymous questionnaire with open-ended questions. Results. There were 355 study participants, 329 (92.7%) females and 26 (7.3%) males. The patients who experienced at least one osteoporotic fracture (n = 208) were significantly less adherent to the therapy, less engaged in sports and regular physical activities, and more prone to nutrition with inadequate intake of calcium and vitamin D than patients without fractures (n = 147). Conclusion. The effectiveness of osteoporosis treatment is decreased by several drug-related problems encountered by both physicians and patients. However, the majority of the drug-related problems could be greatly influenced by appropriate educational programs. [Projekat Ministarstva nauke Republike Srbije, br. 175007]

Background/Aim. Increasing epidemiological studies suggest the association between psoriasis and metabolic syndrome. The aim of this study was to assess the association of metabolic syndrome and its components with psoriasis in a sample of patients from Montenegro, and to predict the factors that determine the metabolic syndrome. Methods. A case-control study was conducted at the Clinic of Dermatology and Venereology, Clinical Center of Montenegro, Podgorica, Montenegro, between January and December 2012. The study group included 101 patients with psoriasis (cases) and 126 patients with the diagnosis of dermatological disease other than psoriasis (controls) consecutively admitted to the same clinic. Results. Metabolic syndrome was more prevalent in the psoriasis patients than in the controls (48.5% vs 20.6%; OR = 2.99). In addition, the psoriasis patients were significantly more likely to be smokers (OR = 2.16) and were less physically active (OR = 0.58). Conclusion. The results of this study demonstrate a strong association between psoriasis and metabolic syndrome independent of psoriasis severity. Patients with psoriasis should be routinely screened for metabolic syndrome and its components. [Projekat Ministarstva nauke Republike Srbije, br. 175025: Clinical-epidemiological research of diseases of public health importance in Serbia]

Background/Aim. Benign prostatic hyperplasia (BPH) is one of the most common disease among males aging 50 years and more. The rise of the prevalence of BPH is related to aging, and since duration of life time period has the tendency of rising the prevalence of BPH will rise as costs of BPH treatment will and its influence on health economic budget. Dutasteride is a new drug similar to finasteride, inhibits enzyme testosterone 5-alpha reductase, diminish symptoms of BPH, reduce risk of the complications and increases quality of life in patients with BPH. But, the use of dutasteride is limited by its high costs. The aim of this study was to compare cost effectiveness of dutasteride and finasteride from the perspective of a purchaser of health care service (Republic Institute for Health Insuranse, Montenegro). Меthods. We constructed a Markov model to compare cost effectivenss of dutasteride and finasteride using data from the available pharmacoeconomic literature and data about socioeconomic sphere actual in Montenegro. A time horizon was estimated to be 20 years, with the duration of 1 year per one cycle. The discount rate was 3%. We performed Monte Carlo simulation for virtual cohort of 1,000 patients with BPH. Results. The total costs for one year treatment of BPH with dutasteride were estimated to be 6,458.00 € which was higher comparing with finasteride which were 6,088.56 €. The gain in quality adjusted life years (QALY) were higher with dutasteride (11.97 QALY ) than with finasteride (11.19 QALY). The results of our study indicate that treating BPH with dutasteride comparing to finasteride is a cost effective option since the value of incremental cost-effectiveness ratio (ICER) is 1,245.68 €/QALY which is below estimated threshold (1,350.00 € per one gained year of life). Conclusion. Dutasteride is a cost effective option for treating BPH comparing to finasteride. The results of this study provide new information for health care decision makers about treatment of BPH in socioeconomic environment which is actual both in Montenegro and other countries with a recent history of socioeconomic transition.

Background/Aim. Delirium is an acute or subacute, and most frequently reversible syndrome of higher cortical functions disturbances that is manifested as generalized disorder. If not prevented, it is associated with various adverse outcomes. The aim of this study was to determine the connection between the markers of inflammation and lethal outcome in patients diagnosed with delirium, hospitalized in the psychiatric intensive care unit. Methods. This retrospective study included 120 patients hospitalized in the psychiatric intensive care unit in whom examination of differences in inflammation markers was done. The examinees have been divided into two groups: the case group of 40 patients who died during the hospitalization, and the control group of 80 examinees who were discharged with the diagnosis Post delirium status. The following variables were taken into account: age, gender, clinical diagnosis of infection (pneumonia and urinary tract infection), laboratory parameters (total of white blood cells, granulocytes, monocytes, C-reactive protein − CRP) and type of delirium (withdrawal or organic). Results. The average age of patients was 50.3 ± 13.1 years. The patients who survived delirium, were on the average 10.5 years younger than the deceased (p < 0.001). More than half (57.5%) of the deceased had pneumonia. There was a statistically significant correlation between pneumonia and lethal outcome in the patients with delirium (p < 0.001). The examinees with lethal outcome had significantly higher median CRP levels than the group of examinees who survived (75.6% ± 54.0 vs 30.3 ± 42.5 ng/L, p < 0.001). Conclusion. Aiming to better and more precise diagnostics of this complicated and still unclear neuropsychiatric syndrome it would be useful to consider introduction of more precise diagnostic algorithms in every unit of intensive care. That would significantly reduce the number of delirium diagnosis overlook, decrease complication of clinical features and would also reduce the unfavorable outcome rate, therefore the total cost of treatment.

Background/Aim. Based on numerous studies in animals, the most prominent toxic effects of decabrominated diphenyl ether (BDE-209) are observed in the liver, thyroid hormone homeostasis, reproductive and nervous systems. BDE-209 exhibits its toxic effects partly through the aryl hydrocarbon (Ah) receptor and consequent induction of hepatic microsomal enzymes. The aim of this study was to assess the hepatotoxic effect vs target tissue dose of BDE-209 in the subacutely orally exposed Wistar rats. Methods. Effects were examined on male Wistar rats, weighing 200-240 g, exposed to doses of 1,000, 2,000 or 4,000 mg BDE-209/kg body weight (bw)/day by gavage during 28 days. Animals were treated according to the decision of the Ethics Committee of the Military Medical Academy, No 9667-1/2011. Evaluation of the hepatotoxic effect was based on: relative liver weight water and food intake, biochemical parameters of liver function [aspartate amino transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gama glutamyl transferase (γ-GT)], and oxidative stress parameters in liver homogenates [malondialdehiyde (MDA), superoxide dismutase (SOD), -SH] and morphological and pathohistological changes in the liver. For the assessment of internal dose - response relationship, lower confidence limit of Benchmark dose (BMDL) of 5% or 10% i.e. BMDL5 or BMDL10, were calculated using PROAST software. Results. After the application of 1,000, 2,000 or 4,000 mg BDE-209/kg bw/day, the concentrations of BDE-209 measured in liver were 0.269, 0.569 and 0.859 mg/kg of liver wet weight, (ww) respectively. Internal doses correlated with external (r = 0.972; p < 0.05) according to equation: internal dose (mg BDE-209/kg of liver ww) = 0.0002 x external dose (mg/kg bw/day) + 0.0622. Hepato-toxicity was demonstrated based on significant increase in AST and γ-GT activities and the degree of histopathological changes. The lowest BMDL5 of 0.07228 mg BDE-209/kg of liver ww, correlating to external dose of 39 mg/kg/day, indicated the increase of AST activity as the most sensitive biomarker of BDE-209 hepatotoxicity in subacutely exposed rats. Conclusion. The results of the present work add up to the issue of BDE-209 toxicity profile with a focus on relationship between internal dose and hepatotoxicity. Critical internal dose for the effect on AST of 0.07 mg/kg of liver ww, corresponding to external dose of 39 mg/kg/day, is the lowest dose ever observed among the studies on BDE-209 hepatotoxicity. For the persistent substances with low absorption rate such as BDE-209, critical effect based on internal dose in majority of cases is considered as more precisely defined than the effect established based on external dose, particularly. [Projekat Ministarstva nauke Republike Srbije, br. III 46009]

Background/Aim. Femoropopliteal bypass is a revascularization technique of lower extremities with excellent outcome. The great saphenous vein is the best graft material, but if it is not adequate or has been removed, synthetic grafts are an useful alternative. Graft occlusion is the most significant complication with the most serious consequences. The aim of this study was to analyse predictive factors for the synthetic femoropopliteal bypass occlusions. Methods. This retrospective case-control study included all patients who underwent synthetic femoropopliteal bypass due to peripheral arterial occlusive disease at the Vascular Surgery Center, Clinical Center of Kragujevac, Serbia, from 2007 to 2013. The cases group were the patients with femoropopliteal graft occlusion (n = 44), with the control group consisted of the patients without such an outcome (n = 88). Results. Significant effects to occlusion were: concomitant cardiovascular disease (adjustedOR 27.05; 95% CI 4.74; 154.35), a type of femoropopliteal bypass (adjustedOR 16.50; 95% CI 4.05; 67.24), previous vascular intervention (adjustedOR 4.67; 95% CI 1.20; 18.14), clinical stage of the disease (adjustedOR 3.73; 95% CI 1.94; 7.18), administration of postoperative oral anticoagulant therapy (adjustedOR 0.05; 95% CI 0.01; 0.23) and the use of angiotensin converting enzyme inhibitors (adjustedOR 0.14; 95% CI 0.03; 0.70). A significant synergism was shown for the following combinations of the observed risk factors: type of femoropopliteal bypass and cardiovascular disease, type of femoropopliteal bypass and previous vascular intervention, previous vascular intervention and cardiovascular disease, previous vascular intervention and beta blockers, cardiovascular disease and diabetes, type of femoropopliteal bypass and antiaggregant therapy, clinical stage of disease and cardiovascular disease, previous vascular intervention and antiaggregant therapy. Conclusion. Concomitant cardiovascular disease, belowknee femoropopliteal bypass, advanced stage of vascular disease and non-use of anticoagulant therapy and angiotensin-converting enzyme inhibitors are the significant predictors of graft occlusion after synthetic femoro-popliteal bypass. Their synergistic effect determines the importance of diabetes, use of beta blockers and platelet antiaggregant therapy. [Projekat Ministarstva nauke Republike Srbije, br. 175007]

Background/Aim. Severe dental anxiety (SDA) is the most severe form of dental anxiety, thus the aim of this study was to determine the factors associated with SDA in students of health-related disciplines. Methods. In this case-control study the cases were students with severe dental anxiety. The study was conducted at the Faculty of Medical Sciences, University of Kragujevac, Serbia. The participants were undergraduate students attending lectures during spring semester 2010/2011 (n = 1,812). A random sample of 800 students was assessed for the association between various risk factors and the severe dental anxiety. The main outcome measures were the data on demographics, dental anxiety, habits concerning oral hygiene, nutrition, general anxiety and (co)morbidity which were collected from the study participants by semi-structured questionnaire. Results. Less frequent visits to the dentist (OR adjusted = 7.02 [2.65; 18.60]) and visiting the dentist only when there is a dental problem (OR adjusted = 8.08 [1.28; 50.93]) were associated with severe dental anxiety. The same was true for improper oral hygiene (OR adjusted = 4.25 [1.16; 15.60]). Factors as changing toothbrush more frequently (OR adjusted = 0.33 [0.14; 0.76]) and having chronic disease (OR adjusted = 0.01 [0.00; 0.09]) were inversely associated with severe dental anxiety. The level of education of students was not associated with severe dental anxiety. Conclusion. Inappropriate oral hygiene, less frequent changes of a toothbrush and less frequent visits to the dentist are important risk factors for severe dental anxiety. [Projekat Ministarstva nauke Republike Srbije, br. 175007]

Background/Aim. Developmental disorders of teeth are the problems that are becoming more present in pediatric dentistry, especially on first permanent molars and incisors. Molar Incisor Hypomineralization (MIH) is proposed term for this phenomenon. The aim of this study was to establish the MIH prevalence in children living in the Foča municipality (Bosnia and Herzegovina) as well as to assess characteristics and expression of hypomineralization within the tested population. Methods. A total of 141 children from the Foča municipality, 8 years of age, were included in this study. Criteria according to Weerhejm have been used for diagnosis of hypomineralization: demarcated opacity (DO), post-eruptive breakdown (PEB), atypical restoration (AR), extracted molars due to MIH (E-MIH) and unerupted tooth (UT). Level and the prominence of color changes have been determined for patients with DO, PEB and AR. Results. MIH in this area was present in 12.8% of children. The prevalence of MIH changes expressed in percentages was as follows: DO was at 9.2%, PEB in 3.5%, AR in 5.6%, while E-MIH was 5.6%. A total of 9.9% of the examinees had mild, 5.6% moderate, and 7.8% severe form of MIH. White form of MIH defects was found in 9.9% of the examinees, white-yellow one in 5.6% and yellow-brown color in 3.5% of the examined children. These changes were more often present in the lower jaw (60.3%). In total, 6.4% of children had these changes present only on molars, while 6.4% of them both on molars and incisors simultaneously. Conclusion. A total of 12.8% of the examinees with MIH is not to be disregarded. With timely diagnosis, prevention and therapy complications could be avoided or mitigated.

Background/Aim. Health education plays a very important role in maintaining health of individuals. Good oral health, as a part of general health, is largely dependent on the level of knowledge, attitudes and habits that children already have. The aim of this study is to examine the level of knowledge and habits in children regarding oral hygiene, diet and bad habits. Methods. The study included 506 school children aged 12 and 15 years in three towns (Foča, Čajniče, Kalinovik, Bosnia and Herzegovina). The survey was conducted in order to assess knowledge, attitudes and habits that children have in relation to their own oral health. Results. Most respondents stated that they began to brush their teeth at the age of 4, while a smaller number linked beginning of tooth brushing to the start of school. The parents more often help the boys during tooth brushing. A total of 54.9% of children brush their teeth after every meal, while 40.1% of them brush teeth only once during the day. Twelve year olds brush their teeth more often, especially after a meal. A total of 92.5% of children had never used fluoride tablets nor are the tablets recommended to them by anyone. More than half of the children (61.7%) visited the dentist for the first time before starting school that is on the regular examination that is performed upon enrollment to school. A pain as a reason for dental visits was present in 43.9%, while the preventive check in only 31.4% of the children. Conclusion. Children included in this study, particularly 15-year-olds, are quite well informed about teeth brushing frequency and proper selection of tools for hygiene maintenance, but this knowledge is not applied. Girls are more responsible for their own health, and come regularly to the preventive dental checkups.

Background/Aim. Recent studies have shown that biological treatments for rheumatoid arthritis can change the course of rheumatoid arthritis and improve functional ability of patients with rheumatoid arthritis. In spite of this fact, use of biological therapy is still limited by high prices of these medicines, especially in countries in socioeconomic transition. The aim of our study was to compare costeffectiveness of a combination of tocilizumab and methotrexate with methotrexate alone for rheumatoid arthritis in Serbia, a country in socioeconomic transition. Methods. For the purpose of our study we designed a Markov model using data on therapy efficacy from the available literature, and data on the costs of health states calculated from records of actual patients treated in the Clinical Center Kragujevac, Serbia. The duration of one cycle in our model was set at one month, and the time horizon was 480 months (40 years). The study was done from the social perspective, and all the costs and outcomes were discounted for 3% per year. Results. Treating rheumatoid arthritis with diseasemodifying antirheumatic drugs (DMARDs) alone was more cost-effective in comparison with a combination of biologic treatment with tocilizumab and DMARDs. The total costs for treating a patient with DMARDs for one year were on average 261,945.42 RSD, or 2,497.70 Euro and the total costs for treatment with tocilizimab plus DMARDs were on average 1,959,217.44 RSD, or 18,659.20 Euro. However, these results are susceptible to changes in costs and treatment effects of tocilizumab in patients with more severe forms of rheumatoid arthritis. Conclusion. Our results show that the use of tocilizumab for rheumatoid arthrits in economic environment of Serbia is not cost-effective. Use of tocilizumab for treating rheumatoid arthritis can become affordable, if costs of its use become lower. In order to start using expensive biologic medicines in patients in transitional countries, special strategy and pricing policy of international pharmaceutical companies are necessary, which would include calculation of prices of biologic medicines on the basis of local pharmacoeconomic studies. [Projekat Ministarstva nauke Republike Srbije, br. 175007]

Background/Aim. Acne is well recognized condition that adversely affects quality of life (QoL) of the patients. The aim of this study was to determine the self-reported prevalence of acne and its main characteristics in high school pupils, and to assess their QoL. Methods. The cross-sectional study conducted in May 2011 comprised 440 pupils from Serbia (281 from Belgrade and 159 from Užice). Participation in the study was voluntary and anonymous. Two questionnaires were administered: a short demographic questionnaire, and Children's Dermatology Life Quality Index (CDLQI). Internal consistency was assessed using the Cronbach’s alpha while item-total score correlations were assessed using Spearman's correlation analysis. Results. The majority of the study population (84.3%) were girls, and 15.7% were boys. The total mean age of the pupils was 16.48 ± 0.55 years. A total of 228 (51.8%) pupils self-reported their acne with significantly higher prevalence in Užice (73.6%) than in Belgrade (39.5%). The mean CDLQI score was 3.55 with the similar quality of life impairment in adolescents from the two cities. The mean Cronbach’s alpha was 0.83. There was a statistically significant positive correlation between the mean overall CDLQI score and CDLQI subscale scores that ranged from 0.401 to 0.841. Conclusion. Our study confirmed that acne is associated with impairment in QoL that is in accordance with previous studies performed on teenagers. The CDLQI is a reliable and valid measure, and can be used as a practical tool for measuring the impact of acne on patients’ QoL. [Projekat Ministarstva nauke Republike Srbije, br. 175025: Clinical-epidemiological research of diseases of public health importance in Serbia]

Background/Aim. Rhabdomyolysis (RM) is potentially lethal syndrome, but there are no enough published data on its frequency and characteristics in acute poisonings. The aim of this study was to determine the causes and severity of RM in acute poisonings. Methods. Patients hospital charts were retrospectively screened during a one-year period in order to identify patients with RM among 656 patients treated due to acute poisonings with different agents. All the patients with RM were selected. Entrance criterion was the value of creatine kinase (CK) over 250 U/L. The severity of RM was assessed according to the Poison Severity Score. The patients were divided into three groups: the first one with mild RM (CK from 250 to 1,500 U/L), the second with moderate RM (CK from 1,500 to 10,000 U/L) and the third with severe RM (CK greater than 10,000 U/L). Results. RM occurred in 125 (19%) of the patients with acute poisonings. It was mainly mild (61%), or moderate (36%), and only in 3% of the patients was severe RM. The incidence of RM was the highest in poisonings with opiates (41%), pesticides (38%), neuroleptics (26%), anticonvulsants (26%), ethyl alcohol (20%), and gases (19%). Psychotropic agents were the most common causes of poisoning, and consequently of RM. Fatal outcomes were registered in 32 (25.60%) of all RM patients. The incidence of fatal outcomes in poisonings with mild, moderate and severe RM was 19.73%, 31.11% and 75%, respectively. Conclusion. RM syndrome occurs at a relatively high rate in acute poisonings. Although agent’s toxicity is crucial for the outcome, severe RM and its complications may significantly influence the clinical course and prognosis of poisoning. Routine analysis of CK, as a relevant marker for RM may indicate the development of RM in acute poisoning and initiate prompt therapeutic measures in preventing acute renal failure as the most frequent consequence of extensive rhabdomyolysis.

Background/Aim. Acne is a common problem in adolescent children with considerable emotional and psychological effects. The aim of this study was to determine the self-reported prevalence of acne and to assess its impact on the quality of life in high school pupils in Serbia. Methods. The cross-sectional study was conducted in May 2011 in two medical high schools in Serbia. Only pupils who gave a written informed consent to participate in the study (n = 440) were asked to fill in two questionnaires: short demographic questionnaire and Cardiff Acne Disability Index (CADI), a disease-specific questionnaire measuring disability induced by acne. Internal consistency (tested by Cronbach’s alpha) and item-total score correlations (Spearman's correlation analysis) were used for reliability analyses. Results. The study population consisted of 440 pupils, 281 from Belgrade and 159 from Užice. Among them 371 (84.3%) were girls and 69 (15.7%) boys, with similar sex distribution in Belgrade and Užice. The total mean age of pupils was 16.48 years (SD = 0.55). Out of 440 pupils 228 (51.8%) self-reported their acne. The acne prevalence was significantly higher in pupils from Užice (73.6%) than in those from Belgrade (39.6%). The overall mean CADI score for the whole sample was 2.87 ± 2.74, with the similar quality of life impairment in adolescents from Belgrade and from Užice. The mean Cronbach’s alpha was 0.82. Conclusion. This study shows that the quality of life impairment due to acne is mild for the majority of the affected pupils. The Serbian version of the CADI is a reliable, valid, and valuable tool for assessing the impact of acne on the quality of life.

Background/Aim. Peri-implantitis presents inflammatory process that affects soft and hard supporting tissues of osseointegrated implant based on inflammatory osteoclastogenesis. The aim of this study was to investigate whether receptor activator of nuclear factor kappa B (RANK) concentrations in peri-implant crevicular fluid could be associated with clinical parameters that reflect inflammatory nature of peri-implantitis. Methods. The study included 67 patients, 22 with diagnosed peri-implantitis, 22 persons with healthy peri-implant tissues and 23 patients with periodontitis. Clinical parameters from each patient were recorded and samples of peri-implant/gingival crevicular fluid were collected for the enzyme-linked immunosorbent assay (ELISA) analysis. Results. RANK concentration was significantly increased in samples from the patients with periimplantitis when compared to healthy implants (p < 0.0001), where the average levels were 9 times higher. At the same time RANK concentration was significantly higher in periimplantitis than in periodontitis sites (p < 0.0001). In implant patients pocket depths and bleeding on probing values were positively associated with high RANK concentrations (p < 0.0001). Conclusion. These results revealed association of increased RANK concentration in samples of periimplant/ gingival crevicular fluid with peri-implant inflammation and suggests that RANK could be a pathologic determinant of peri-implantitis, thereby a potential parameter in assessment of peri-implant tissue inflammation and a potential target in designing treatment strategies.

Introduction. Almost all individual antipsychotics are classified into the intermediate pregnancy risk category as no or limited data exist about human pregnancy outcomes. We presented the case of zuclopenthixol decanoate using in two successive pregnancies of the same woman, which had not been published in the available peer-reviewed literature. Case report. A middle-age female subject who suffered from schizophrenia received zuclopenthixol decanoate injection during her two consecutive pregnancies. About four and a half months before diagnosis of the first pregnancy (~3.5 years after psychosis emergence), zuclopenthixol decanoate (400 mg every other week, im injection) was introduced to the treatment protocol (due to previous non-compliance with haloperidol and risperidone). A significant clinical improvement was achieved and the dose during pregnancy was reduced to 200 mg once monthly and maintained to date. In both pregnancies the women gave birth to healthy girls who have been developing normally until now, at their ages of 6 months and of 3.5 years. During pregnancy and after giving birth to children the mothers’ psychiatric status and her social functioning were significantly improved and are still stable. Close monitoring of the mother’s health, a multidisciplinary approach to both her treatment and the monitoring of pregnancies as well as the complete compliance with the prescribed drug protocol were likely to be crucial for the therapeutic success. Conclusion. A favorable outcome of the present case suggests that the zuclopenthixol decanoate is a rational therapeutic option for pregnant women suffering from psychosis when the expected benefit exceed the potential risk, but a definitive evidence for its safety requires large, controlled studies. [Projekat Ministarstva nauke Republike Srbije, br. 175014]

Background/Aim. Reliable and comparable analysis of health risks is an important component of evidence-based and preventive programs. The aim of this study was to analyze the impact of the most relevant avoidable risk factors on the burden of the selected conditions in Serbia. Methods. Attributable fractions were calculated from the survey information on the prevalence of a risk factor and the relative risk of dying if exposed to a risk factor. The population-attributable risks were applied to deaths, years of life lost due to premature mortality (YLL), years of life with disability (YLD) and disability adjusted life years (DALY). Results. More than 40% of all deaths and of the total YLL are attributable to cigarette smoking, overweight, physical inactivity, inadequate intake of fruit and vegetables, hypertension and high blood cholesterol. Alcohol consumption has in total a beneficial effect. According to the percent of DALY for the selected conditions attributable to the observed risk factors, their most harmful effects are as follows: alcohol consumption on road traffic accidents; cigarette smoking on lung cancer; physical inactivity on cerebrovascular disease (CVD), ischemic heart disease (IHD) and colorectal cancer; overweight on type 2 diabetes; hypertension on renal failure and CVD; inadequate intake of fruit and vegetables on IHD and CVD, and high blood cholesterol on IHD. Conclusions. This study shows that a high percentage of disease and injury burden in Serbia is attributable to avoidable risk factors, which emphasizes the need for improvement of relevant preventive strategies and programs at both individual and population levels. Social preferences should be determined for a comprehensive set of conditions and cost effectiveness analyses of potential interventions should be carried out. Furthermore, positive measures, derived from health, disability and quality of life surveys, should be included. [Projekat Ministarstva nauke Republike Srbije, br. 175042]

Introduction. Caffeine is indicated in the treatment of migraine headaches, as well as neonatal apnea and bradycardia syndrome. In mild poisoning, the most prevalent symptoms are nausea, vomiting, diarrhea, tremor, anxiety and headache. In more severe cases, symptoms consist of heart rythym abnormalities, myocardial infarction and seizures. Due to its common lipolytic effect, caffeine is used in mesotherapy, usually in combination with drugs of similar effect. We presented a patient with acute iatrogenic caffeine poisoning. Case report. A 51-year-old woman, with preexisting hypertension and hypertensive cardiomyopathy was subjected to cosmetic treatment in order to remove fat by intradermal caffeine injections. During the treatment the patient felt sickness, an urge to vomit, and a pronounced deterioration of general condition. Upon examination, the patient exhibited somnolence, hypotension and nonsustained ventricular tachycardia, which was sufficient enough evidence for further hospitalization. On admission to the intensive care unit the patient was anxious with increased heart rate, normotensive, with cold, damp skin, and visible traces of injection sites with surrounding hematomas on the anterior abdominal wall. Paroxysmal supraventricular tachycardia (PSVT) on electrocardiographic monitoring was found. The laboratory analysis determined a lowered potassium level of 2.1 mmol/L (normal range 3,5 - 5.2 mmol/L), and a toxicological analysis (liquid chromatography with ultraviolet detection) proved a toxic concentration of caffeine in plasma - 85.03 mg/L (toxic concentration over 25 mg/L). On application of intensive therapy, antiarrhythmics, and substitution of potassium, as well as both symptomatic and supportive therapy, there was a significant recovery. The patient was discharged without any sequele within four days. Conclusion. A presented rare iatrogenic acute caffeine poisoning occured due to massive absorption of caffeine from the subcutaneous adipose tissue into the circulation when injected directly into the tiny blood vessels, as evidenced by hematoma formation. Poisoning manifestations were registered in gastrointestinal, CNS (anxiety, somnolence) and cardiovascular (hypotension, ventricular tachycardia and nonsustained PSVT) system. In this era of mesotherapeutic treatment promotion, one should keep in mind toxic prevention, with application being carried out exclusively in a specialized institution

Background/Aim. Spinal cord injuries (SCI) could be associated with a significant functional impairment in the areas of mobility, self-care, bowel and bladder emptying and sexuality. The aim of this study was to compare demographic characteristics and functional outcomes of nontraumatic and traumatic spinal cord injury patients. Methods. This study was designed as retrospective case series study. A detailed medical history including sex, age, mode of trauma, and clinical and radiological examination was taken for all patients. Hospital records were used to classify the patients according to the following: mechanism of injury, neurological level of injury, functional outcomes, associated injuries, method of treatment, secondary complications and length of stay. The following clinical scores were measured in the patients: American Spinal Injury Association standards (CASTA), Functional Independence Measure (FIM), and Modified Aschworth score (MAS). Results. Out of totally 441 patients with spinal cord injury, 279 were traumatic patients (TSCI) and 162 nontraumatic patients (NTSCI); 322 men and 119 women. The mean age of the patients was 46.1 ± 19.9 years. Traumatic and nontraumatic populations showed several significant differences with regard to age, level and severity of lesion. When adjusted for these factors patients with traumatic injuries showed a significantly lower FIM score at admission and significantly better improvement in the FIM score at discharge. The two populations were discharged with similar functional outcome. Conclusions. The NTSCI patients in our study were younger, more frequently female, with less complications before rehabilitation and less frequently treated operatively than the TSCI patients. Hospital rehabilitation of the TSCI patients was longer than that of the NTSCI patients, but their functional gain from admission was also higher, so at discharge. Traumatic and nontraumatic spinal cord lesion patients achieved similar results in regard to neurological and functional status.